title: Potential of recombinant inorganic pyrophosphatase antigen as a new vaccine candidate against Baylisascaris schroederi in mice.
abstract: The intestinal nematode Baylisascaris schroederi is an important cause of death for wild and captive giant pandas. Inorganic pyrophosphatases (PPases) are critical for development and molting in nematode parasites and represent potential targets for vaccination. Here, a new PPase homologue, Bsc-PYP-1, from B. schroederi was identified and characterized, and its potential as a vaccine candidate was evaluated in a mouse challenge model. Sequence alignment of PPases from nematode parasites and other organisms show that Bsc-PYP-1 is a nematode-specific member of the family I soluble PPases. Immunohistochemistry revealed strong localization of native Bsc-PYP-1 to the body wall, gut epithelium, ovary and uterus of adult female worms. Additionally, Bsc-PYP-1 homologues were found in roundworms infecting humans (Ascaris lumbricoides), swine (Ascaris suum) and dogs (Toxocara canis). In two vaccine trials, recombinant Bsc-PYP-1 (rBsc-PYP-1) formulated with Freund complete adjuvant induced significantly high antigen-specific immunoglobulin (Ig)G but no IgE or IgM responses. Analysis of IgG-subclass profiles revealed a greater increase of IgG1 than IgG2a. Splenocytes from rBsc-PYP-1/FCA-immunized mice secreted low levels of T helper (Th)1-type cytokines, interferon-γ and interleukin (IL)-2, while producing significantly high levels of IL-10 and significantly elevated levels of IL-4 (Th2 cytokines) after stimulation with rBsc-PYP-1 in vitro. Finally, vaccinated mice had 69.02-71.15% reductions (in 2 experiments) in larval recovery 7 days post-challenge (dpc) and 80% survival at 80 dpc. These results suggest that Th2-mediated immunity elicited by rBsc-PYP-1 provides protection against B. schroederi, and the findings should contribute to further development of Bsc-PYP-1 as a candidate vaccine against baylisascariasis.
authors.affiliation: Department of Parasitology, College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China. guangyou1963@aliyun.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xie
authors.forename: Sijie
authors.initials: S
authors.lastname: Chen
authors.forename: Yubo
authors.initials: Y
authors.lastname: Yan
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Desheng
authors.initials: D
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Chengdong
authors.initials: C
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Nong
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Gu
authors.forename: Shuxian
authors.initials: S
authors.lastname: Wang
authors.forename: Xuerong
authors.initials: X
authors.lastname: Peng
authors.forename: Guangyou
authors.initials: G
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017191:Ascaridida Infections / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D001199:Ascaridoidea / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D043564:Inorganic Pyrophosphatase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013047:Specific Pathogen-Free Organisms; D014612:Vaccines / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; D015801:Helminth Proteins; D011994:Recombinant Proteins; D014612:Vaccines; D043564:Inorganic Pyrophosphatase